Exploiting Gene-Expression Deconvolution to Probe the Genetics of the Immune System

Yael Steuerman, Irit Gat-Viks

Research output: Contribution to journalArticlepeer-review

Abstract

Sequence variation can affect the physiological state of the immune system. Major experimental efforts targeted at understanding the genetic control of the abundance of immune cell subpopulations. However, these studies are typically focused on a limited number of immune cell types, mainly due to the use of relatively low throughput cell-sorting technologies. Here we present an algorithm that can reveal the genetic basis of inter-individual variation in the abundance of immune cell types using only gene expression and genotyping measurements as input. Our algorithm predicts the abundance of immune cell subpopulations based on the RNA levels of informative marker genes within a complex tissue, and then provides the genetic control on these predicted immune traits as output. A key feature of the approach is the integration of predictions from various sets of marker genes and refinement of these sets to avoid spurious signals. Our evaluation of both synthetic and real biological data shows the significant benefits of the new approach. Our method, VoCAL, is implemented in the freely available R package ComICS.

Original languageEnglish
Article numbere1004856
JournalPLoS Computational Biology
Volume12
Issue number4
DOIs
StatePublished - Apr 2016

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